Ikeguchi Masahide, Hirooka Yasuaki, Kaibara Nobuaki
First Department of Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Cancer. 2002 Nov 1;95(9):1938-45. doi: 10.1002/cncr.10898.
The suppression of apoptosis is an important factor in tumor progression in hepatocellular carcinoma (HCC). However, to the authors knowledge the clinicopathologic importance of the expression of apoptosis-related genes (bcl-2, bax, and survivin) in HCC remains unclear. In the current study, the authors investigated the correlation between expression of apoptosis-related genes and the occurrence of spontaneous apoptosis in HCC. In addition, the prognostic significance of the expression of apoptosis-related genes in patients with HCC was analyzed.
Tissue samples were obtained through surgical resection of the liver in 53 patients with HCC and 5 patients without HCC. The expression levels of bcl-2, bax, survivin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA were analyzed using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The bcl-2/bax ratio and survivin/GAPDH ratio of the tumors were compared with clinicopathologic findings. In addition, apoptotic tumor cells and the proliferative activity of tumor cells were detected using immunohistochemistry.
The bcl-2/bax ratios of the tumors were not different from those of noncancerous liver tissue samples obtained from regions distant from the tumors and were not found to correlate with apoptosis or with clinical importance in HCC. In contrast, the survivin/GAPDH ratios of the tumors were significantly higher than those of noncancerous liver tissue and demonstrated a negative correlation with apoptosis and a positive correlation with the proliferative activity of tumor cells. Moreover, patients who had tumors with a high survivin/GAPDH ratio were found to have a high incidence of disease recurrence.
The real-time RT-PCR method appears to be a useful technique with which to detect reliable gene expression in tissues, and the detection of survivin mRNA expression by this method may be a useful marker for identifying patients with HCC who have a high risk of disease recurrence.
凋亡抑制是肝细胞癌（HCC）肿瘤进展的一个重要因素。然而，据作者所知，凋亡相关基因（bcl-2、bax和survivin）在HCC中的表达的临床病理重要性仍不清楚。在本研究中，作者调查了凋亡相关基因表达与HCC中自发凋亡发生之间的相关性。此外，还分析了凋亡相关基因表达在HCC患者中的预后意义。
通过手术切除肝脏，获取53例HCC患者和5例非HCC患者的组织样本。使用实时逆转录聚合酶链反应（RT-PCR）分析bcl-2、bax、survivin和甘油醛-3-磷酸脱氢酶（GAPDH）mRNA的表达水平。将肿瘤的bcl-2/bax比值和survivin/GAPDH比值与临床病理结果进行比较。此外，使用免疫组织化学检测凋亡肿瘤细胞和肿瘤细胞的增殖活性。
肿瘤的bcl-2/bax比值与从远离肿瘤的区域获取的非癌肝组织样本的比值没有差异，并且未发现与HCC中的凋亡或临床重要性相关。相反，肿瘤的survivin/GAPDH比值显著高于非癌肝组织，并且与凋亡呈负相关，与肿瘤细胞的增殖活性呈正相关。此外，发现survivin/GAPDH比值高的肿瘤患者疾病复发率高。
实时RT-PCR方法似乎是一种用于检测组织中可靠基因表达的有用技术，通过该方法检测survivin mRNA表达可能是识别具有高疾病复发风险的HCC患者的有用标志物。
